Abstract: Abstract: Objective　To investigate the relationship between methylation of methylenetetrahydrofolate reductase (MTHFR) promoter and diabetic nephropathy. Methods　According to the staging criteria of chronic kidney disease, 81 patients with diabetic nephropathy (the nephropathy group) were divided into the stage 1-2 group (26 cases), the stage 3a-3b group (39 cases) and the stage 4-5 group (16 cases). Another 139 patients with simple type 2 diabetes were used as the simple diabetes group and 51 healthy volunteers were used as the control group. The serum levels of MTHFR promoter methylation, triacylglycerol (TG), homocysteine (Hcy), glycosylated hemoglobin (HbA1c), urinary microalbumin and estimated glomerular filtration rate (EGFR) were detected in the three groups. The differences in these indicators were compared between groups. Logistic regression and ROC curve were used to analyze the relationship between MTHFR gene promoter methylation and diabetic nephropathy in patients with type 2 diabetes mellitus. Results　Compared with the control group, the level of MTHFR promoter methylation was decreased in the nephropathy group and the simple diabetes group (P＜0.05). Compared with the simple diabetes group, the level of MTHFR promoter methylation was decreased in the nephropathy group (P＜0.05). The levels of MTHFR promoter methylation decreased successively in the stage 1 to 2 group, the stage 3a to 3b group and the stage 4-5 group (P＜0.05). Multivariate Logistic regression analysis showed that hypertension and high level of urinary microalbumin were risk factors of diabetic nephropathy in patients with type 2 diabetes, and the high level of eGFR and methylation of MTHFR gene were protective factors of diabetic nephropathy in type 2 diabetes (P＜0.05). Compared with methylation of MTHFR gene, urinary microalbumin and eGFR alone, the parallel examination of three indexes had a higher diagnostic efficiency, better sensitivity and specificity. Conclusion　The level of MTHFR promoter methylation in patients with diabetes is decreased, and it is associated with the occurrence of diabetic nephropathy and the aggravation of disease severity in type 2 diabetes patients.

Key words:  diabetes mellitus, type 2, diabetic nephropathies, methylenetetrahydrofolate reductase (NADPH2), DNA methylation, urine microalbumin, estimated glomerular filtration rate